NEUROPATHOLOGY CORE (CORE D) - PROJECT SUMMARY The Neuropathology Core of the Wisconsin ADRC (ADRC) will support cutting edge cellular and molecular neuroscience technologies to the ADRC patient population and their properly banked tissue in the service of enhancing research regarding early detection, treatment outcome, and basic mechanisms of AD. The core will facilitate clinical-pathologic and translational research on normal aging, mild cognitive impairment (MCI), AD and other dementias by providing to Wisconsin ADRC and outside investigators a comprehensive resource of biospecimens, biomarker data, clinical data, and state-of-the-art diagnoses for MCI and AD, vascular, Lewy body, TDP-43, and mixed pathologies, from subjects in the Clinical Core and the Wisconsin Registry for Alzheimer's Prevention (WRAP). The Neuropathology Core will generate and assemble critical diagnostic information by combining clinical data (Core B), innovative neuroimaging (Core G) and biomarker assays collected during life with brain autopsy and morphologic, immunohistochemical, genetic, cell and molecular post-mortem analyses. The Neuropathology Core will also provide access to cutting edge tools (including genomics and proteomics) to enhance AD research on banked, frozen tissue. The Core will accomplish these goals by 1) collecting and archiving ante-mortem CSF, blood and DNA and post-mortem frozen and fixed tissue blocks from multiple brain regions on deceased individuals who are enrolled in the Wisconsin ADRC as well as normal elderly controls; 2) providing state-of-the-art postmortem diagnoses on Clinical Core subjects, collect NACC neuropathology data and make the results available to the family, relevant clinicians, qualified researchers, & NACC; 3) distributing ante-mortem and post-mortem biospecimens (brain, CSF, blood products, and DNA) and neuropathologic, genetic, biomarker and other data to suit the requirements of qualified research projects, both within UW-Madison and for national and international multi-center collaborations; 4) performing genetic and biomarker analyses in support of ADRC and outside investigators; and 5) providing high quality, cost effective, cell and molecular neuroscience equipment, technology, assays, expertise, and training to Wisconsin ADRC investigators. A flow of services is therefore envisaged whereby Wisconsin ADRC investigators and collaborators are able to obtain unambiguous post-mortem diagnosis, neuropathological data and tissues from the Neuropathology Core together with comprehensive biomarker data (Biomarker Services) and neuroimaging data (Core G). Moreover, advanced molecular and cellular analyses can be performed on tissues by the Biomarker, and Cellular and Molecular Neuroscience Services.